Nanofluidic applications, integrated with microfluidics have immense opportunities for tuning optical properties and manipulating small molecules such as proteins and DNA. Various techniques have been developed to fabricate nanometer-scale channels. Previously, electron beam lithography, focused ion beam milling techniques, interference lithography, and nano imprint lithography have been developed to pattern nano-scale trenches for this purpose. Alternate non-lithographic approaches have also been introduced to produce nanochannels (D. Huh, K L. Mills, X. Zhu, M. A. Burns, M. D. Thouless, S. Takayama, Nature Materials, 6, 624 (2007); S. Chung, J H. Lee, M-W. Moon, J. Han, R. D. Kamm, Advanced Materials, 20, 3011 (2008)).
Recently a number of nanofluidic fabrication techniques have been introduced that exploit the deformability of elastomeric materials like polydimethylsiloxane (PDMS). These techniques are limited in the complexity of the devices which can be fabricated, being able to only create straight or irregular channels normal to the direction of an applied strain.
Of the many reasons why nanofluidic systems are of interest, the most well developed applications revolve around sensing, detection, and species handling in single or “few” molecule environments (Hong J W, Quake S R (2003) Integrated nanoliter systems. Nature Biotechnol 21: 1179-1183; Tegenfeldt J O, et al. (2004) The Dynamics of Genomic-Length DNA Molecules in 100-nm Channels. Proc Natl Acad Sci USA 101: 10979-10983; Han J, Craighead H G (2000) Separation of Long DNA Molecules in a Microfabricated Entropic Trap Array. Science 288: 1026-1029; Fu J, Schoch R B, Stevens A L, Tannenbaum S R, Han J (2007) A patterned anisotropic nanofluidic sieving structure for continuous-flow separation of DNA and proteins. Nature Nanotech 2: 121-128; Austin R (2007) Nanofluidics: A fork in the nano-road. Nature Nanotech 2: 79-80; Riehn R, et al. (2005) Restriction mapping in nanofluidic devices. Proc Natl Acad Sci USA 102: 10012-10016; Daiguji H, Yang P, Szeri A J, Majumdar A (2004) Electrochemomechanical Energy Conversion in Nanofluidic Channels. Nano Lett 4: 2315-23211 Cowan M L, et al. (2005) Ultrafast memory loss and energy redistribution in the hydrogen bond network of liquid H2O. Nature 434: 199-202).
Researchers have recently demonstrated unique bioanalytical capabilities in nanofluidic devices including the ability to elongate single DNA molecules (Tegenfeldt J O, et al. (2004) The Dynamics of Genomic-Length DNA Molecules in 100-nm Channels. Proc Natl Acad Sci USA 101: 10979-10983), concentrate protein samples by more than four orders of magnitude (Lee J H, Chung S, Kim S J, Han J (2007) Poly(dimethylsiloxane)-Based Protein Preconcentration Using a Nanogap Generated by Junction Gap Breakdown. Anal Chem 79: 6868-6873) and to efficiently separate both large (Han J, Craighead H G (2000) Separation of Long DNA Molecules in a Microfabricated Entropic Trap Array. Science 288: 1026-1029; Chou H-P, Spence C, Scherer A, Quake S (1999) A microfabricated device for sizing and sorting DNA molecules. Proc Natl Acad Sci USA 96: 11-13) and small (Fu J, Schoch R B, Stevens A L, Tannenbaum S R, Han J (2007) A patterned anisotropic nanofluidic sieving structure for continuous-flow separation of DNA and proteins. Nature Nanotech 2: 121-128) biomolecules.
As a result of their technological promise, numerous methods have been developed to fabricate these systems including: electron beam lithography (Reccius C H, Stavis S M, Mannion J T, Walker L P, Craighead H G (2008) Conformation, Length, and Speed Measurements of Electrodynamically Stretched DNA in Nanochannels. Biophys J 95: 273-286; Mannion J T, Reccius C H, Cross J D, Craighead H G (2006) Conformational Analysis of Single DNA Molecules Undergoing Entropically Induced Motion in Nanochannels. Biophys J 90: 4538-4545), focused ion beam milling (Cao H, et al. (2002) Fabrication of 10 nm enclosed nanofluidic channels. Appl Phys Lett 81: 174-176), interference lithography (O'Brien II M J, et al. (2003) Fabrication of an integrated nanofluidic chip using interferometric lithography. J Vac Sci Technol B 21: 2941-2945), AFM lithography (Pellegrino L, et al. (2006) (Fe,Mn) 3O4 Nanochannels Fabricated by AFM Local-Oxidation Nanolithography using Mo/Poly(methyl methacrylate) Nanomasks. Adv Mater 18: 3099-3104) and nano-imprint lithography (Tegenfeldt J O, et al. (2004) The Dynamics of Genomic-Length DNA Molecules in 100-nm Channels. Proc Natl Acad Sci USA 101: 10979-10983; Xia Q, Morton K J, Austin R H, Chou S Y (2008) Sub-10 nm Self-Enclosed Self-Limited Nanofluidic Channel Arrays. Nano Lett 8: 3830-3833). The significant advantages of these high-end nanofabrication technologies are their high resolution, reproducibility and flexibility.
In spite of these advantages, these methods are somewhat limited to provide rapid prototyping of the nanofluidic systems. To augment these high-resolution techniques, several groups have developed nanofluidic fabrication in PDMS using lower resolution lithography methods. Huh et al. (Huh D, et al. (2007) Tuneable elastomeric nanochannels for nanofluidic manipulation. Nature Mater 6: 424-428) for example used crack formation in a surface oxide layer to make nanochannels with mechanically tunable widths. Similarly Chung et al. (Chung S, Lee J H, Moon M-W, Han J, Kamm R D (2008) Non-Lithographic Wrinkle Nanochannels for Protein Preconcentration. Adv Mater 20: 3011-3016) utilized wrinkles on an elastomeric PDMS surface which when bonded to another surface formed discrete nanochannels. While these approaches greatly simplify the fabrication of nanochannels, the complexity of the devices which can be created is relatively low, in that only straight lines orthogonal to the stretching force can be fabricated.
An additional challenge of nanofluidic fabrication with soft materials like PDMS is the relatively low stiffness of the material resulting in dimensional instability and even channel collapse to the point of sealing (Chou S Y, Krauss P R, Renstrom P J (1996) Imprint Lithography with 25-Nanometer Resolution. Science 272: 85-87). With the goal of determining the design rules which minimize these effects, Huang et al. (Huang Y Y, et al. (2005) Stamp Collapse in Soft Lithography. Langmuir 21: 8058-8068.; Zhou W, et al. (2005) Mechanism for stamp collapse in soft lithography. Appl Phys Lett 87: 251925-3) recently reported on the mechanism of channel collapse (also referred to as “roof” or “stamp” collapse) in soft lithography. Their work characterized many of the conditions under which the middle of a suspended channel structure will sag to the point of touching the lower (channel) substrate and permanently seal. Ultimately, the use of PDMS with higher stiffness or channels designs with a close to square cross section have been found to be good techniques to minimize these problems (Huh D, et al. (2007) Tuneable elastomeric nanochannels for nanofluidic manipulation. Nature Mater 6: 424-428; Thangawng A L, Swartz M A, Glucksberg M R, Ruoff R S (2007) Bond-Detach Lithography: A Method for Micro/Nanolithography by Precision PDMS Patterning. Small 3: 132-138; Kang H, Lee J, Park J, Lee H H (2006) An improved method of preparing composite poly(dimethylsiloxane) moulds. Nanotechnology 17: 197-200).
There is therefore a need in the art for methods for fabricating nanofluidic devices that use deformable elastomeric materials and that create complex nanochannel structures.
Citation or identification of any reference in Section 2, or in any other section of this application, shall not be considered an admission that such reference is available as prior art to the present invention.